GPR119 agonists for the treatment of type 2 diabetes

• Published in: Expert opinion on therapeutic patents Vol. 19; no. 10; p. 1339
• Main Authors: Jones, Robert M, Leonard, James N, Buzard, Daniel J, Lehmann, Juerg
• Format: Journal Article
• Language: English
• Published: England 01.10.2009
• Subjects: Animals; Blood Glucose - drug effects; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Drug Design; Drug Therapy, Combination; Humans; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - therapeutic use; Incretins - metabolism; Insulin - metabolism; Molecular Structure; Patents as Topic; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - metabolism; Signal Transduction - drug effects; Structure-Activity Relationship; Treatment Outcome
• ISSN: 1744-7674
• DOI: 10.1517/13543770903153878

Diabetes is a chronic disease that occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces. Hyperglycemia, or raised blood sugar, is a common effect of uncontrolled diabetes and over time leads to serious damage to many of the body's systems, especially nerves and blood vessels. Diabetes causes about 5% of all deaths globally each year and is likely to increase by > 50% in the next 10 years without urgent action. In light of these alarming statistics, the pharmaceutical industry has been on a quest to characterize more promising molecular targets to satisfy stringent new criteria for anti-hyperglycemic agents introduced by the American Diabetes Association. On to this stage, G-protein-coupled receptor 119 (GPR119) has emerged as arguably one of the most exciting targets for the treatment of type 2 diabetes mellitus in the new millennium. In this review, we outline the current clinical trial landscape and paint a detailed illustration of the key structural information realized from GPR119 agonist campaigns that have recently emerged in the Patent Cooperation Treaty literature. GPR119 agonists mediate a unique nutrient-dependent dual elevation of both insulin and glucagon like peptide 1/glucose-dependent insulinotropic peptide levels in vivo. As a stand-alone therapy or in tandem with approved DPP-IV inhibitors, they could herald a brand new treatment paradigm for type 2 diabetes mellitus. With the passage of the first GPR119 agonist clinical candidates into Phase I trials (Arena/Ortho McNeil APD597; Metabolex MBX-2982; Prosidion/OSI PSN821) and confirmatory reports of clinical proof of concept with respect to glycemic control and incretin release, the spotlight has been set for this new class of therapeutic.